Charcot–Marie–Tooth disease: Inherited neuropathies revisited

摘要

More than 120 years have elapsed since the French physicians Jean-Martin Charcot and Pierre Marie (Charcot and Marie, 1886) and the Englishman Howard Henry Tooth (Tooth, 1886) directed the interest of the neurological community to a distal limb muscleatrophy, which turned out to be the most common neuromuscular disorder in humans affecting no less than 1 in 2500 individuals throughout Europe and the US (Skre, 1974). This early period of research was later highlighted by a remarkable phenotypic convergence and the observation that both axonal and demyelinating lesions resulted in a similar clinical presentation, namely a motor and sensory neuropathy with distal predominance (Keller and Chance, 1999). Familial segregation quickly identified the majority of ‘Charcot–Marie–Tooth’ (CMT) cases as inherited and more than 40 genes have now been associated with perturbation of myelin compaction and maintenance, cytoskeletal abnormalities and axonal transport disorders, as well as malfunction of mitochondrial replication and intracellular trafficking – all leading to a similar clinical phenotype ( Pareyson et al., 2009 D. Pareyson, C. Marchesi and E. Salsano, Hereditary predominantly motor neuropathies.